Anticoagulants and Antiplatelet Drugs

Question 1

Factor IIa Inhibitors

Answer 1

Unfractionated Heparin*
Dabigatran
Fondaparinux

Question 2

Heparin Site of Action

Answer 2

Combines with antithrombin III (ATIII) to inactivate active clotting factors (IIa, IXa, Xa, XIa, XIIa)

Question 3

LMWHs/ Fondaparinux Site of Action

Answer 3

Combine with antithrombin III (ATIII) to inactivate Xa

Question 4

Hirudin, Dabigatran Site of Action

Answer 4

Directly inactivate IIa (thrombin)

Question 5

Rivaroxaban Site of Action

Answer 5

Directly inactivates Xa

Question 6

Venous Thrombi Composition

Answer 6

Composed mainly of fibrin and trapped red blood cells with relatively few platelets

Question 7

Atrial Thrombi Composition

Answer 7

Composed mainly of platelet aggregates held together by small amounts of fibrin

Question 8

Anticoagulant Agent Uses

Answer 8

Drugs of choice for prevention and treatment of venous thromboembolism and for prevention of cardioembolic events in patients with atrial fibrillation. Anticoagulants are also effective for arterial thrombosis and their effects can be additive with antiplatelet agents

Question 9

Antiplatelet Agent Uses

Answer 9

Drugs of choice primarily for prevention and treatment of arterial thrombosis (primary and secondary prevention and treatment of acute coronary syndrome).

Question 10

Primary Prevention of ACS

Answer 10

W/ Risk Factors: Use Aspririn

W/O Risk Factors: Apsirin for Men >45 and women above >65

Question 11

Secondary Prevention

Answer 11

Recent MI → Aspirin (clopidogrel if aspirin intolerant)

Ischemic Stroke → Aspirin + clopidogrel

Question 12

UA/NSTEMI Treatment

Answer 12

Asprin
± clopidogrel
± UFH, LMWH or fondaparinux
± GPIIb/IIIa inhibitor

Question 13

Acute MI (STEMI) Treatment

Answer 13

Aspirin + clopidogrel
+ UFH, LMWH or fondaparinux
+ GPIIb/IIIa inhibitor

Question 14

PCI Treatment

Answer 14

Aspirin + clopidogrel
+ UFH, LMWH or fondaparinux
+ GPIIb/IIIa inhibitor

Question 15

AFib Treatment

Answer 15

Warfarin or dabigatran or rivaroxaban or apixaban

(aspirin can be used for patients at low risk)

Question 16

Venous Thromboembolism (VTE) Treatment

Answer 16

LMWH or UFH or

fondaparinux + warfarin

Question 17

VTE Prevention

Answer 17

1) Hospitalized/Gen Surgery - Low-dose UFH or LMWH or fondaparinux
2) Ortho Surgery - Fondaparinux or rivaroxaban or dabigatran or LMWH or warfarin

Question 18

PAD Treatment

Answer 18

Aspirin (clopidogrel if aspirin intolerant)

Question 19

aPTT is used to monitor?

Answer 19

Heparin therapy (not significantly affected by LMWHs)

Question 20

Heparin Mechanism

Answer 20

Binds to Antithrombin III (AT III) and increases its activity 1000 fold. Inhibits factors 2, 9, 10, 11, 12 and 13.

Question 21

LMWH (Enoxapirin) and Fondaparinux Mechanisms

Answer 21

• Bind to AT III and inactivate factor Xa, but not IIa (thrombin)
• Claimed to have equal efficacy as regular heparin for VTE with less tendency for bleeding complications and less effects on platelets (i.e.,thrombocytopenia)

Question 22

Direct Thrombin IIa Inhibitors

Answer 22

Argatroban, bivalirudin, lepirudin, desirudin- all given parenterally

Question 23

Heparin & Derivative Pharmacokinetics

Answer 23

Not absorbed in GI Tract
Given Paranterally w/ IV Loading dose
Drug of choice if pregnant
FIRST ORDER RENAL ELIMINATION!!

Question 24

LMWH vs Heparin

Answer 24

LMWH Generally preferred due to less variable response (no monitoring needed) and less thrombocytopenia
Adjunct treatment in unstable angina/ acute MI

Question 25

Heparin/ Derivatives Adverse Rxns

Answer 25

Hemorrhage is the chief complication Hypersensitivity Thrombocytopenia Osteoporosis

Question 26

Heparin & LMWH Overdosage Sign and Treatment

Answer 26

Bleeding is the chief sign | GIVE PROTAMINE!!

Question 27

Warfarin Mechanism

Answer 27

Acts in liver to prevent synthesis of clotting factors. Does not work until clotting factors are turned over.

Question 28

Warfarin Targets

Answer 28

Vitamin K-dependent clotting factors (II, VII, IX, X and Ca2+ dependent factors)

Question 29

Warfarin Uses

Answer 29

AFib | Prophylaxis/ treatment of thromboembolism

Question 30

Warfarin Adverse Rxns

Answer 30

``` Hemorrhage Necrosis of fatty soft tissue (use heparin bridge) GI Issues Osteoporosis DON'T USE IF PREGNANT! ```

Question 31

Warfarin Overdose Signs and Treatments

Answer 31

Signs: Hematuria, excessive menorrhagia, gum bleeding Major Bleeding- Hold warfarin, administer 5-10 mg of Vitamin K IV. Also use Prothrombin complex concentrate (PCC)

Question 32

Dabigatran Mechanism

Answer 32

Acts in the plasma to directly inhibit the activity of thrombin (Factor IIa). Does NOT require frequent monitoring and dosage adjustments. NO ANTIDOTE!

Question 33

Dabigatran Pharmacokinetic

Answer 33

Absorbed as a prodrug (etexilate) and converted to active form by plasma and liver esterases. Excreted renally.

Question 34

Dabigatran Uses

Answer 34

AFib!

Question 35

Dabigatran Adverse Rxns

Answer 35

Bleeding in 17% of pt's (3% w/ major bleeding event) GI Complaints Fewer DDI than warfarin Anticoagulant effect is IRREVERSIBLE!

Question 36

Antiplatelet Agents

Answer 36

Aspirin Clopidogrel Dipyridamole Abciximab/ Eptifibatide/ Tirofiban

Question 37

Aspirin Mechanism

Answer 37

Small dose (40-80 mg) inhibits COX-1 synthesis of thromboxane in platelets. Largest [acetylsalicyclic acid] is in the portal vein so highest effect on circulating COX-1 (not tissue COX-2)

Question 38

Clopidogrel Mechanism

Answer 38

ADP (purinergic-P2Y12) receptor antagonists that interfere with ADP-induced platelet aggregation. Clopidogrel is prodrug converted to active metabolite by CYP450, which then irreversibly inhibits receptor.

Question 39

Dipyridamole Mechanism

Answer 39

Blocks phosphodiesterase breakdown of cAMP, elevating cAMP levels and potentiating prostacyclin’s anti-aggregatory action. Combined with aspirin as Aggrenox. Little or no apparent benefit as antithrombotic agent.

Question 40

Abciximab/Eptifibatide/Tirofiban Mechanism

Answer 40

Blocks IIb/IIIa receptors on platelet thus preventing integrin and fibrinogen binding that facilitates aggregation (platelet-platelet binding). Advantage of blocking all pathways of platelet activation.

Question 41

What antiplatelet agent(s) is/are dosed intravenously?

Answer 41

Abciximab, Eptifibatide, Tirofiban

Question 42

Clopidogrel Adverse Rxns

Answer 42

GI upset, headache, dizziness, upper respiratory infection, bleeding; concomitant use of proton pump inhibitors (PPIs) may inhibit activation of clopidogrel by CYP2C19

Question 43

Prasugrel and Ticagrelor Adverse Rxns

Answer 43

Bleeding!

Question 44

GIIb/IIIa inhibitor Adverse Rxns

Answer 44

Bleeding!

Question 45

Acute MI Anti-platelet drugs

Answer 45

Aspirin (chewed and swallowed) plus ADP antagonist

Question 46

Unstable Angina Anti-platelet drugs

Answer 46

Aspirin ± ADP antagonist

Question 47

Percutaneous Coronary Interventions (PCI) Anti-platelet drugs

Answer 47

Aspirin plus ADP antagonists ± GIIb/IIIa inhibitors

Question 48

Secondary Prevention of Acute MI Anti-platelet Drugs

Answer 48

Aspirin!

Question 49

Secondary Prevention of Ischemic Stroke Anti-platelet Drugs

Answer 49

Aspirin ± dipyridamole

Question 50

Anticoagulants we need to know

Answer 50

Heparin (UFH) / enoxaparin (LMWH), warfarin, dabigatran, rivaroxaban

Question 51

Antiplatelet agents we need to know

Answer 51

Aspirin, clopidrogel, GIIB/IIIa inhibitors (as class: abciximab / eptifibatide / tirofiban)

Question 52

Thrombolytic Agents we need to know

Answer 52

Tissue Plasminogen Activator (tPA) and variants